Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.
Replicated association between an IL28B gene variant and a sustained response to pegylated interferon and ribavirin.
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DOI：
10.1053/j.gastro.2010.02.009
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发表时间：
2010-06
期刊：
影响因子：
29.4
通讯作者：
McHutchison JG
中科院分区：
文献类型：
--
作者：
McCarthy JJ;Li JH;Thompson A;Suchindran S;Lao XQ;Patel K;Tillmann HL;Muir AJ;McHutchison JG
慢性丙型肝炎病毒（HCV）感染的患者用聚乙二醇干扰素和利巴韦林（PEG-IFN/RBV）治疗，其在不到50%的HCV基因型1感染者中有效。全基因组关联研究已经将对PEG-IFN/RBV的应答与19号染色体上IFN-λ基因附近的常见单核苷酸多态性联系起来。我们调查了多态性rs 12979860和治疗反应之间的关联在一个不同的队列慢性丙型肝炎患者。采用来自杜克肝病临床研究数据库和生物储存库的1021例连续患者的数据进行横断面研究。我们分析了DNA、临床和人口统计学数据，沿着231例受试者对PEG-IFN/RBV应答的有效数据。该研究包括高加索人（n=178），非洲裔美国人（n=53）和HCV基因型1（n=186）和2/3（n=45）。检测rs 12979860基因型与持续病毒学应答的相关性，持续病毒学应答定义为治疗结束后24周检测不到HCV RNA水平。rs 12979860 CC基因型（在约40%的白人中发现）预测了白人对治疗的持续病毒学应答（比值比5.79; 95%置信区间2.67-12.57; p=9.0 × 10-6），与HCV基因型和其他协变量无关。Rs 12979860 CC预测HCV基因型1感染患者的持续应答特异性为78%，敏感性为65%-优于HCV基因型（目前用于预测治疗应答）。rs 12979860基因型是慢性HCV感染患者对PEG-IFN/RBV应答的重要独立预测因子;该基因型的检测可用于确定考虑抗病毒治疗的患者的最佳治疗疗程。
Patients with chronic hepatitis C virus (HCV) infections are treated with pegylated interferon and ribavirin (PEG-IFN/RBV), which is effective in less than 50% of those infected with HCV genotype 1. Genome-wide association studies have linked response to PEG-IFN/RBV with common single nucleotide polymorphisms in the vicinity of IFN-λ genes on chromosome 19. We investigated the association between the polymorphism rs12979860 and treatment response in a diverse cohort of chronic HCV patients. A cross-sectional study was performed using data from 1021 consecutive patients enrolled in the Duke Hepatology Clinic Research Database and Biorepository. We analyzed DNA, clinical, and demographic data, along with validated data of the response of 231 subjects to PEG-IFN/RBV. The study included Caucasians (n=178), African Americans (n=53), and HCV genotypes 1 (n=186) and 2/3 (n=45). The rs12979860 genotype was tested for an association with sustained virologic response, defined as undetectable levels of HCV RNA 24 weeks after treatment ended. The rs12979860 CC genotype (found in ~40% of Caucasians) predicted a sustained virologic response to therapy among Caucasians (odds ratio 5.79; 95% confidence interval 2.67–12.57; p=9.0 × 10-6), independent of HCV genotype and other covariates. Rs12979860 CC predicted a sustained response with 78% specificity and 65% sensitivity in patients infected with HCV genotype 1—better than HCV genotype (currently used to predict treatment response). rs12979860 genotype is a significant independent predictor of response to PEG-IFN/RBV in patients with chronic HCV infection; tests for this genotype might be used to determine the best course of treatment for patients considering antiviral therapy.
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影响因子：
2
作者：
PIEGORSCH, WW;WEINBERG, CR;TAYLOR, JA
通讯作者：
TAYLOR, JA
影响因子：
158.5
作者：
Alter, MJ;Kruszon-Moran, D;Margolis, HS
通讯作者：
Margolis, HS
DOI：
10.1016/s1050-3862(98)00019-9
发表时间：
1999-02-01
期刊：
GENETIC ANALYSIS-BIOMOLECULAR ENGINEERING
影响因子：
--
作者：
Livak, KJ
通讯作者：
Livak, KJ
影响因子：
4.8
作者：
Zhu H;Butera M;Nelson DR;Liu C
通讯作者：
Liu C
影响因子：
39.2
作者：
Armstrong, Gregory L.;Wasley, Annemarie;Alter, Miriam J.
通讯作者：
Alter, Miriam J.